Summary of work: The neuroanatomic and neurophysiologic underpinnings of age- associated cognitive and memory change remain unclear, as there is little information on longitudinal brain changes. We are performing annual magnetic resonance imaging (MRI), positron emission tomography (PET), and neuropsychological assessments in participants from the Baltimore Longitudinal Study of Aging (BLSA), aged 55 and older, to investigate the neurobiological basis of memory change. These evaluations will allow us to examine changes in brain structure and function which may be early predictors of cognitive change and impairment, including Alzheimers Disease. An understanding of these associations and early detection of brain changes will be critical in identifying individuals likely to benefit from new interventions. In addition, we are using neuroimaging tools to investigate brain changes in response to estrogen and testosterone therapy in older women and men. These studies are a follow-up to our observations that estrogen may protect against memory change and Alzheimers Disease in post- menopausal women. In a study of 119 right-handed participants (68 men, 51 women) aged 56-85 from the Baltimore Longitudinal Study of Aging, accuracy and response time in verbal and figural tasks were measured during PET. Patterns of relative cerebral blood flow of radioactively labeled water were analyzed by Statistical Parametric Mapping. There were no differences between men and women in the verbal recognition task, but women were significantly more accurate than men on the figural recognition task. Both tasks elicited increases in relative cerebral blood flow in the right inferior and middle frontal lobes, bilateral visual association, and cerebellar regions. In men, verbal recognition was uncorrelated with blood flow. In women, verbal recognition accuracy was significantly correlated with blood flow in the bilateral visual association, cerebellar, and occipito-temporal regions, and the right inferior frontal region. These findings suggest that men and women may use different task-specific strategies in performing these tasks. Men perform better using a visual strategy to remember non-verbalizable designs. Women perform better using an analytic approach that may require greater left hemisphere processing.Recent studies suggest that estrogen replacement (ERT) may protect against normal age-associated memory decline and Alzheimers disease (AD). In contrast, the apolipoprotein E (apoE) allele is a genetic risk for AD and possibly for memory decline in nondemented individuals. We examined the effects of apoE genotype and ERT use in 184 women aged 50-89 in the Baltimore Longitudinal Study of Aging, 103 of whom were ERT users. Groups were matched on education, income, health, and verbal ability. ERT users had significantly better verbal learning and short- and long-delay recall than nonusers. The same pattern of results was found in a subgroup of 99 women with apoE data. ERT was associated with enhanced verbal memory in women with and without an E4 allele, and the magnitude of the ERT benefit was the same regardless of genotype. ApoE genotype had no effect on any cognitive measure. These results suggest that ERT has a significant and selective benefit on memory in nondemented women regardless of their apoE4 status. - brain aging, cognition, memory, MRI, PET, longitudinal studies, estrogen - Human Subjects & Human Subjects: Interview, Questionaires, or Surveys Only